Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: Involvement of the transcription factor Nrf2

Vittorio Calabrese, Agrippino Ravagna, Claudia Colombrita, Giovanni Scapagnini, Eleonora Guagliano, Menotti Calvani, D. Allan Butterfield, Anna Maria Giuffrida Stella

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Efficient functioning of maintenance and repair processes seem to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, under control of several genes termed vitagenes. These include members of the heat shock protein system, and there is now evidence that the heat shock response contributes to establishing a cytoprotective state in a wide variety of human conditions, including inflammation, neurodegenerative disorders, and aging. Among the various heat shock proteins, heme oxygenase-1 has received considerable attention; it has been recently demonstrated that heme oxygenase-1 induction, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. Acetyl-L-carnitine is proposed as a therapeutic agent for several neurodegenerative disorders. Accordingly, we report here that treatment of astrocytes with acetyl-L-carnitine induces heme oxygenase-1 in a dose- and time-dependent manner and that this effect was associated with up-regulation of heat shock protein 60 as well as high expression of the redox-sensitive transcription factor Nrf2 in the nuclear fraction of treated cells. In addition, we show that addition of acetyl-L-carnitine to astrocytes, prior to proinflammatory lipopolysaccharide- and interferon-γ-induced nitrosative stress, prevents changes in mitochondrial respiratory chain complex activity, protein nitrosation and antioxidant status induced by inflammatory cytokine insult. Given the broad cytoprotective properties of the heat shock response, molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, manipulation of endogenous cellular defense mechanisms via acetyl-L-carnitine may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. We hypothesize that maintenance or recovery of the activity of vitagenes may delay the aging process and decrease the risk of age-related diseases.

Original languageEnglish
Pages (from-to)509-521
Number of pages13
JournalJournal of Neuroscience Research
Issue number4
StatePublished - Feb 15 2005


  • Acetyl-L-carnitine
  • Antioxidant defenses
  • Heme oxygenase
  • Mitochondrial dysfunction
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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